First and second window of protection of pre-ischemic vagal stimulation on myocardial infarction in mice

KELLY J; MÉNDEZ DIODATI N; FRANCO RIVEROS V; BERNATENÉ E; VERÓNICA CASANOVA; BUCHHOLZ B; GELPI RJ

Buenos Aires

Congreso; Reunión conjunta de Sociedades de Biociencias; 2017

We have previouslyproven that vagal stimulation (VS) decreases infarct size (IS) when appliedbefore ischemia, thus mimicking classic preconditioning. Our objective was tostudy the chronology and mechanisms of the protective effect of VS, and toassess whether the protection is comprised of a first and second window. Micewere randomly assigned to different protocols (n=5-7 per group). The control grouphad 30 min of regional myocardial ischemia and 2 h of reperfusion (I/R). Theother groups consisted of 10 min of pre-ischemic VS (pVS) and different timesof recovery between VS and I/R protocol: 5 min, 3-6-12-24-48-72-96 h. The 5 min,3 h and 72 h groups were redone to administer a muscarinic receptor inhibitor(atropine). pVS-5min and pVS-72h were given a mitochondrial K+ ATP channelblocker (5-HD) and a nitric oxide synthase inhibitor (L-NAME). All animals werecatheterized to measure ventricular function. Hearts were dyed with Evans Blue andincubated in TTC to measure IS. pVS-5min had smaller IS in comparison to I/R(44±3% and 57±2%, respectively; p<0.05). pVS-3hs and pVS-6hs had a deeper ISreduction (34±3% and 34±3%, respectively; p<0.05 vs pVS-5min). Cardioprotectionwas lost at 12, 24 and 48 h post-VS (56±4%, 53±2%, 56±2%, respectively; p=NS vsI/R). Later at 72 h post-VS, cardioprotection reappeared (42±4%; p<0.05 vs pVS-48h)but was lost at 96 h post-VS (56±3%; p=NS vs I/R). The IS-reducing effect ofpVS-5min, 3 and 72 h was abolished by atropine (56±2%, 56±3% and 56±3%; p=NS vsI/R), 5-HD in pVS-5min and 72 h (55±2% and 62±5%, p=NS vs I/R) and L-NAME in pVS-5minand pVS-72h (56±3% and 57±2%, p=NS vs I/R). In conclusion, VS has twoprotection windows similar to classic preconditioning. The first window lasts 6h and the second window appears at 72 h and is lost at 96 h. The mechanismsunderlying the cardioprotective effect include muscarinic receptors,mitochondrial K+ ATP channels and nitric oxide synthase.